Clozaril and Treatment-Resistant Schizophrenia

The Tirat Carmel Mental Health Center in Israel is sponsoring important research into treatment-resistant schizophrenia. Poor response to medication and therapy is very common with schizophrenia. The reasons for treatment resistance are numerous, including medication avoidance, physical illness, and comorbid psychiatric conditions. Researchers believe that a person’s genes may also be involved in how he or she responds to medications. Geneticists have already identified several gene sequences that may control how the body metabolizes medication. Empirical research in the form of clinical trials is the missing link that will connect theory with practice. The Israeli scientists hope the current trial will enhance our understanding of treatment-resistant schizophrenia and possibly develop some alternative therapies.

Participants in the study will receive a twice-daily dose of Clozaril (clozapine) 150 mg. Clozaril has a well-established history of being an effective and relatively safe “last line” option for schizophrenic individuals. The medication is often prescribed after a suicide attempt or violent outburst and when all other options have failed. Doctors will carefully monitor individual progress for three months and make any needed changes to dosages. After three months, individuals who have achieved a sustained remission will be eligible for inclusion in the analysis. Those who required additional medications or didn’t respond to Clozaril will not be eligible. Likewise, those deemed too ill to legally give their informed consent will not be included in the study.

Researchers want to understand what variables lead to satisfactory drug response in this sample of treatment-resistant schizophrenic people. They will approach this question on two fronts. First, blood tests will reveal the concentration of Clozaril in the plasma. Doctors don’t yet have a firm grasp on the ideal blood plasma concentration needed for the drug to be effective. Different people metabolize medicine at different rates. It’s likely that different people need different levels of the drug in their system to see the effects. Still, there’s likely a minimum amount under which there can be no therapeutic effect. Researchers will also take the genetic profile of each participant. They will look for correlations between certain genetic types and blood plasma concentration.

The current research into treatment-resistant schizophrenia will move us closer to the ultimate goal of personalized medicine. When all other factors are accounted for, a clear understanding of how genes and medicine interact within the body will make life better for those with all kinds of illnesses, not just schizophrenia.


  1. Clozapine – PubMed Health. (n.d.). National Center for Biotechnology Information. Retrieved August 24, 2012, from
  2. Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Schizophrenic Patients. (n.d.). Retrieved August 24, 2012, from

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